Diabetes mellitus develops spontaneously in aging Macaca nigra. The disease is associated with a lesion in the islets of Langerhans in which secretory cells deteriorate and the protein amyloid is deposited. As monkeys age, the hormonal and islet aberrations become worse and eventually there is impaired hormone secretion, glucose intolerance, and hyperglycemia. These changes may be a counterpart to similar events in a significant portion of the aging human diabetic and nondiabetic populations. Antibodies to islet cells (ICA) have been identified in aging prediabetic and diabetic Macaca nigra in association with islet cell degeneration. Prevalence, concentrations, and changes in ICA will be measured in all monkeys, and results will be correlated with islet pathologic changes and metabolic deterioration. A specific subpopulation of human Type II diabetics, clinically analogous to these aging monkeys, were examined for ICA. Initial results showed that 46% have ICA. The prevalence of ICA will be surveyed in a larger population of diabetic and nondiabetic older human beings, and correlations with age, obesity, insulin requirements, severity of diabetes, HLA type, and concurrent autoimmune diseases will be sought. Islet amyloid probably results from an antibody reaction with proteins from degenerating secretory cells. Several different molecular forms appear to be present. A knowledge of the structure of the amyloid would give insight into its source. Homologies will be sought between the amino acid composition and sequence of the islet amyloids and possible sources, such as immunoglobulins and islet hormone and nonhormone proteins. The cause of diabetes in these monkeys is unknown. Since viruses play a major role in the development of human Type I diabetes, monkeys of all ages and of known metabolic and clinical states will be examined for viral involvement. The study of Macaca nigra can explain this form of metabolic impairment and diabetes that has never been well understood in aging human beings.